This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this collaboration is to determine the crystal structure of the tertiary complex of WT hALR2 / nitrile-containing inhibitor / NADP+. hALR2, human aldose reductase, is a 36 kDa aldo-keto reductase that catalyzes the conversion of aldehydes derived from carbohydrate metabolism to corresponding alcohols and is believed to be responsible for many long-term diabetic complications. We have been working on using nitrile-containing hALR2 inhibitors as Stark probes in order to study the electrostatic environment in hALR2. The crystal structure of this tertiary complex will be used to locate the nitrile probe, and to further perform molecular dynamics simulations.